Mucosal impedance measuring apparatus for detecting and measuring the condition of mucosa

ABSTRACT

A mucosal impedance measuring apparatus detects and measures a condition of mucosa. The mucosal impedance measuring apparatus includes a catheter comprising a tube, impedance sensing electrodes on an exterior surface of the catheter, a balloon mounted on the tube in which the balloon is capable of inflation and deflation, and an impedance measuring system. The impedance measuring system is adapted to measure a pressure-regulated impedance measurement of the mucosa that is indicative of the condition of the mucosa when the balloon is inflated and the impedance sensing electrodes direct an electric current through mucosa while the balloon is pressed against the mucosa.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/425,530 entitled “Method of Detecting and Measuring the Condition ofIntraluminal Esophageal Mucosa” filed Feb. 6, 2017, which is adivisional of U.S. patent application Ser. No. 13/182,417 entitled“Display System for Displaying Conditions of Esophageal Mucosa andIndications of Gastroesophageal Reflux Disease” filed Jul. 13, 2011 andissued as U.S. Pat. No. 9,814,408 on Nov. 14, 2017, which claims thebenefit of U.S. Provisional Patent Application No. 61/363,997 entitled“Apparatus and Method for Mucosal Impedance Diagnostic Testing forGastroesophageal Reflux Disease” filed Jul. 13, 2010 and U.S.Provisional Application No. 61/447,605 entitled “Apparatus and Methodfor Measuring Impedance of Esophageal Mucosa” filed Feb. 28, 2011, allof which applications are hereby specifically incorporated herein byreference for all they disclose and teach.

BACKGROUND

Gastroesophageal Reflux Disease is a very common symptom serving as thebasis for 22% of primary care visits. Current estimates are that 14% ofAmericans suffer from Gastroesophageal Reflux Disease on at least aweekly basis. The demographics of Gastroesophageal Reflux Disease haveincreased markedly over the past years as fueled by factors of poordiet, increasing body mass index (BMI), and sedentary lifestyle.

Under the Montreal definition, Gastroesophageal Reflux Disease isdefined as “a condition which develops when the reflux of the stomachcontents causes troublesome symptoms and/or complications.” Esophagealdamage secondary to gastroesophageal reflux can include reflux esophagitis (inflammatory damage of the esophageal lining called mucosa), andBarrett's esophagus, an abnormal change (metaplasia) in the cells of thedistal portion of the esophagus wherein normal squamous epitheliumlining of the esophagus is replaced by metaplastic columnar epithelium.Barrett's esophagus has a strong association with esophagealadenocarcinoma, a particularly lethal cancer. Symptoms are consideredtroublesome if they adversely impact a patient's well-being. Commonsymptoms, which can compromise the patient's well-being, includeheartburn, regurgitation, and chest pain. Atypical symptoms, which cancompromise a patient's well-being, include chronic cough, chronic throatclearing, hoarseness, and respiratory disorders, such as asthma andrecurrent pneumonia.

Gastroesophageal reflux is characterized by bolus movements progressingretrograde from the stomach to the esophagus, which can be detected andmonitored with commercially available multichannel intraluminalimpedance (MU) and acid detecting probes pH inserted through the nose ormouth into the esophagus, such as MU equipment manufactured by SandhillScientific, Inc., of Highlands Ranch, Colo., USA. Reflux esophagi tisand Barrett's esophagus can be detected by endoscopic visual observationand biopsies analyzed by electron microscopy. U.S. Pat. No. 7,818,155,issued to Stuebe et al., which is incorporated herein by reference,teaches detecting reflux and bolus transit in the esophagus with MUequipment and that such detection is enhanced by using a different(lower) impedance baseline in the signal processing for patients withdiseased esophageal tissue than for more healthy patients.

The foregoing examples of related art and limitations related therewithare intended to be illustrative and not exclusive, and they do not implyany limitations on the inventions described herein. Other limitations ofthe related art will become apparent to those skilled in the art upon areading of the specification and a study of the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated herein and form a partof the specification, illustrate some, but not the only or exclusive,example embodiments and/or features. It is intended that the embodimentsand figures disclosed herein are to be considered illustrative ratherthan limiting.

In the drawings:

FIG. 1 is diagrammatic elevation view of an example embodiment of amulti-channel intraluminal impedance catheter with a tube on which theimpedance sensor electrodes are mounted and an inflatable displacingballoon or bladder also mounted on the catheter tube to push the tubeand impedance sensor electrodes to one side of the esophagus intocontact with the mucosal tissue on the interior wall of the esophagus;

FIG. 2 is a diagrammatic illustration of the catheter of FIG. 1 in theesophagus with the balloon or bladder deflated and collapsed forinsertion into, or removal from, the esophagus;

FIG. 3 is an enlarged vertical cross-section of a portion of thecatheter of FIG. 1 illustrating an example structure and displacingballoon or bladder inflation method;

FIG. 4 is an enlarged horizontal cross-section of the catheter of FIG. 1with the balloon or bladder inflated as taken along the section line 4-4in FIG. 3;

FIG. 5 is a function block diagram of an example embodiment of a mucosalimpedance measuring system;

FIG. 6 is a more detailed function block diagram of another exampleembodiment of a mucosal impedance measuring system;

FIG. 7 is a work diagram of one example embodiment of a mucosalimpedance measuring system;

FIG. 8 is a software flow diagram of one example embodiment of a mucosalimpedance measuring system;

FIG. 9 is an example analysis work flow diagram of one exampleembodiment of a mucosal impedance measuring system;

FIG. 10 is a chart of mean mucosal impedance values (in Ohms) forpatients at visually perceptible esophagitis and Barrett's esophagus ascompared to visually normal esophageal mucosa;

FIG. 11 is a chart showing mucosa impedance values (in Ohms) forpatients with visually normal tissue and normal acid exposure and forpatients with visually normal tissue and abnormal acid exposure;

FIG. 12 is a graphical representation of typical impedance value curvesfor healthy mucosal tissue and diseased or damaged mucosal tissue alongthe length of the esophagus;

FIG. 13 is a diagrammatic elevation view of another example embodimentof a mucosal impedance catheter with multiple impedance sensorelectrodes disposed at divers axial and angular locations on aninflatable balloon or bladder that is inflatable to push the impedancesensor electrodes into contact with multiple, divers axial and angularlocations of the mucosal tissue along the length of the esophagus;

FIG. 14 is an enlarged diagrammatic elevation view of the examplemucosal impedance catheter of FIG. 13 illustrating an example structurewith flexible integrated circuit boards comprising the impedance sensorelectrodes mounted on the peripheral surface of the inflatable balloonor bladder;

FIG. 15 is an enlarged diagrammatic elevation view of the examplemucosal impedance catheter of FIG. 13 deflated and collapsed forinsertion into, or extraction from, the esophagus;

FIG. 16 is an enlarged diagrammatic view in longitudinal cross-sectionof the mucosal impedance catheter of FIG. 13 to illustrate an exampleinflatable structure and inflation method; and

FIG. 17 is a diagrammatic view of an example esophageal mucosa mappingdisplay illustrating areas of healthy and damaged mucosa utilizingmucosal impedance data obtained from an esophagus with the multipleaxially and angularly disposed impedance sensor electrodes of theexample mucosal impedance catheter of FIGS. 13-16.

DETAILED DESCRIPTION OF EXAMPLE IMPLEMENTATIONS

An example embodiment of a mucosal impedance catheter 10 for measuringimpedance of esophageal mucosa is illustrated diagrammatically in FIGS.1-4 positioned in an esophagus E with an inflated balloon or bladder 80to push the catheter tube 12 and the mucosal Impedance sensor electrodes40 on the catheter tube 12 into direct contact with the mucosa of theinterior wall 84 of the esophagus E. When the balloon or bladder 80 isexpanded, for example, by inflation, the impedance sensor electrodes 40are pressed against the mucosa on the interior wall 84 of the esophagusE, as illustrated in FIG. 1, displacing air, liquid, bolus remnants orother artifacts (not shown) that may have been between any of theelectrodes 40 and the mucosa. Therefore, such pressing of the sensorelectrodes 40 against the mucosa enhances likelihood of direct contactof the electrodes 40 with the mucosa, which enhances direct, accuratemeasurement of the impedance of the mucosa with little or nointerference from air, liquid, bolus remnants, or other artifacts, thatmay have different impedance values than the mucosa. The catheter tube12 is non-conductive, so it does not affect or interfere withmeasurements of impedance between the electrodes 40.

Measuring intraluminal impedance in the esophagus is well-known topersons skilled in the art, as taught, for example, in U.S. Pat. No.5,109,870, issued to Silny et al., or U.S. Pat. No. 7,818,155, issued toStuebe et al., thus does not need to be described further for purposesof this invention. Suffice it to say that impedance, which is oppositionto flow of electric current, can be measured between any of the contactsor impedance sensor electrodes 40 on the catheter tube 12. While anyimpedance measuring instrumentation and methodology will work, a simpleexample is to provide a constant voltage source connected across a pairof conductive contacts, e.g., any pair of the electrodes 40, to make anelectric current flow between that pair of contacts 40. The current flowcan be measured by an ammeter or similar instrumentation, for example,in the processing electronics 106 shown in FIG. 5. According to Ohm'slaw, the magnitude of the electric current measured is proportional tothe impedance of the material through which the electric current flowsbetween the contact or sensor electrodes 40. Therefore, if the mucosa onthe interior wall 84 of the esophagus E is positioned across any two ofthe contact or sensor electrodes 40 of the catheter 10, as illustratedin FIG. 1, the electric current measured is dependent at least in parton the impedance of the mucosa. On the other hand, if the mucosa is notpositioned across two of the electrodes 40, then the current measurementwill be inversely proportional to the impedance of whatever othermaterial the current has to flow through in order to complete theelectric circuit, e.g., saliva, air, bolus in the esophagus, orwhatever. Therefore, a mechanism, such as the balloon 80 for pushing thecatheter tube 12 and its electrodes 40 against the mucosa of the inneresophageal wall 84, is important to accurate direct impedancemeasurements of the mucosa. The lower the impedance of the materialacross the electrodes 40, the greater the current flow will be, and viceversa. It is also possible to measure the impedance of the mucosa withonly one electrode on the catheter 10 if there is another electrode orcontact in the electric circuit somewhere else on the patient's body(not shown) to complete an electric circuit in a manner that causescurrent to flow through the mucosa from or to the single electrode.However, such single electrode systems may have safety and accuracyissues that are not as easily controllable and manageable as the examplemultiple electrodes 40 on the catheter tube 12 as shown in FIGS. 1-4. Inany event, some current control or limiting device or circuitryconnected to the electrode or electrodes 40 can be used to prevent theflow of too much electric current, which could bum or otherwise injurethe tissue.

The balloon or bladder 80 can be inflated by pressurized air or otherfluid, which can be directed, for example, through the lumen 56 of thetube 12 into the interior space 90 of the balloon or bladder 80, asillustrated by fluid flow arrows 86, 87, 88 in FIGS. 3 and 4. Theballoon or bladder comprises a flexible bag designed to be inflated withair or other gas or liquid, causing it to expand and fill a space thatit otherwise does not fill when deflated and collapsed. Either of theterms balloon or bladder is appropriate for this purpose, and thoseterms may be used interchangeably herein to describe such a component orstructure. Therefore, for convenience, this description will proceedwith the term balloon, but without any intent to limit the scope of thatterm vis-a-vis bladder.

One or more holes 92 in the wall of the tube 12 can be provided to allowthe air or other inflating fluid to flow from the lumen 56 of the tube12 into the balloon 80 to inflate the balloon 80 and then to flow backout of the balloon 80 to deflate the balloon 80. The balloon 80 can beattached to the exterior surface of the tube 12 in any convenient,leak-proof manner, for example, with an adhesive 94, or the tube 12 andballoon 80 can be constructed from or with a single manufacturedcomponent. The balloon 80 can be made of a stretchable, resilientmaterial or of a non-compliant material, such as Mylar™ or any otherminimally conductive or non-conductive material, preferably one thatwill not leak the inflation fluid into the esophagus E. If the balloon80 material is non-stretchable, then it can be sized so that, when it isinflated, it expands only to the extent necessary to push the tube 12and electrodes 40 against the interior wall 84 of the esophagus E, asexplained above, regardless of the pressure of the fluid (within re˜sonso that it does not burst). Enough material to allow expansion of theballoon 80 to a diameter in a range of about 2-3 cm, i.e., the diameterof a typical esophagus E lumen, is generally sufficient. On the otherhand, if the material of the balloon 80 is resiliently stretchable, thenthe pressure of the inflating fluid should be carefully controlled so asto not expand the balloon 80 too much, e.g., not more than the typical2-3 cm diameter of the esophagus E lumen, in order prevent injury to theesophagus E.

The balloon 80 can be built in a manner such that it extends radiallyoutward from a sector of the tube 12, as illustrated in FIG. 4, forexample, a sector in the range of about 45-180 degrees, although thisrange is not critical. Also, while not shown, there can be more than oneballoon 80 mounted on the tube 12 to inflate and extend radially outwardfrom the tube 12. For example, two balloons 80 (not shown) could bemounted side-by-side on the tube 12 so that, together, they could extendfrom 120 degrees and 270 degrees in relation to the impedance sensorelectrodes 40 or at any other angular orientations that effectively pushthe tube 12 and sensor electrodes 40 against the interior wall 84 of theesophagus E. There can also be more than one balloon 80, mounted atdifferent longitudinal positions along the length of the tube 12 insteadof just one balloon.

Each electrode 40 of the example catheter embodiment 10 can be a partialband of electrically conductive material adhered or otherwise attachedto the exterior surface of the catheter tube 12, as best seen in FIGS. 3and 4, although other shapes, for example, buttons or beads, could alsobe used. Insulated wires 83 in a bundle 85 can be used to connect eachelectrode independently to the impedance signal generating andprocessing circuit 106 (FIG. 1) through holes 87 in the tube 12. Thebands of electrodes 40 can extend any convenient amount around peripheryof the tube 12, for example, but not for limitation, in a range of 30 to180 degrees. The goal of electrode shape and sizing is to achieve good,direct contact between the electrodes and the mucosa while minimizing oreliminating direct contact between the electrodes and other matter,e.g., bolus remnants, air, liquid, or other artifacts.

In use, the catheter 10 is inserted through the person's nose or mouth,throat, and upper esophageal sphincter (UES) and into the esophagus Ewith the balloon 80 deflated, as illustrated in FIG. 2, for ease ofinsertion and to prevent injury. For impedance recording, mapping,diagnostic, or other purposes, it may be desirable to know the locationsof the impedance sensor electrodes 40 in the esophagus E when theimpedance of the mucosa is being measured so that the locations whereimpedance measurements of respective channels 48 can be determined forrecording, mapping, diagnostic, and other purposes. For example, but notfor limitation, the impedance sensor electrodes 40 can be mounted onecentimeter apart from adjacent electrodes 40, as shown in FIG. 1, andthe distal-most electrode 40 can be located about one-half of acentimeter above the top of the LES, as also shown in FIG. 1. Witheleven of such electrodes 40 spaced 1.0 centimeter apart, thisarrangement can provide ten impedance channels 48 evenly spaced over aten (10) centimeter length of the esophagus E. Each impedance channel 48measures the impedance of the mucosa between two selected adjacentelectrodes 40. Three of the most distal impedance channels 48 arespecifically identified in FIG. 1, and, in that example spacing, thosethree distal impedance channels 48 are considered to be centered at 1.0cm, 2.0 cm, and 3.0 cm above the top of the LES, respectively. Theremaining, more proximal, impedance channels spanning other pairs ofelectrodes 40 above the distal impedance channels 48 are notspecifically identified with part numbers in FIG. 1, to avoid clutter inthe drawing, but they are addressable electronically for measurementrecording, mapping, etc. Of course, more or fewer electrodes 40, thusimpedance channels 48 can be provided, and the distance betweenelectrodes 40 can be different, depending on the desires of a particularclinician or catheter manufacturer. Therefore, impedances measured withthe electrodes 40 can be related to specific locations, e.g., levels, ofthe esophagus E in relation to the LES.

In FIGS. 1 and 2, an optional pressure sensor 35 is shown at or near thedistal end 60 of the catheter tube 12 for use in positioning thecatheter 10 at a known spatial relationship to the lower esophagealsphincter (LES), where the pressure is normally greater than in theesophagus E above the LES or in the interior cavity C of the stomach Sbelow the LES. The pressure sensed by the optional pressure sensor 35can be monitored for the greatest pressure as the distal end 60 of thecatheter 10 is pushed through the LES and into the stomach S, whereuponthe sensed pressure will fall as the pressure sensor 35 enters theinternal cavity C of the stomach S. Then, the catheter 10 can be pulledupwardly again until that same greatest pressure is observed from thepressure sensor 35, which indicates that the pressure sensor 35 islocated in the LES. Several repetitions of this procedure can be used toensure the desired position is attained.

Another option without having or using the optional pressure sensor 35is to sense the greater pressure of the LES on the distal end 60 of thecatheter tube 12 caused by the LES with an air or fluid pressure sensoror gauge to sense the pressure in the catheter tube 12. For example, thepressure sensor 212 in the air or inflating fluid supply tube 208 shownin FIG. 6, which is connected in fluid-flow relation to the cathetertube 12, can be used to sense the location of the distal end 60 of thecatheter tube 12 in the LES as the distal end 60 is pushed and pulledthrough the LES. Other positioning or locating devices or methods canalso be used.

When the catheter 10 is positioned in the esophagus E as desired, theballoon 80 is inflated with pressurized fluid through the lumen 56 ofthe tube 12, as explained above, to force the tube 12 and impedancesensor electrodes 40 into direct contact with the inside wall 84 of theesophagus E. In that position, the impedance of the mucosa on the insidewall 84 can be measured, as explained above. After the impedancemeasurements are completed, the pressure in the tube 12 is released toatmosphere or a negative pressure (vacuum) can be applied to deflate theballoon 80 before pulling the catheter 10 out of the esophagus E. In oneembodiment, the balloon 80 could also be evacuated with a vacuum pump, areversible pressure pump, or other device to ensure it is completelycollapsed, as explained below, before pulling the catheter 10 out of theesophagus E. Such evacuation may be particularly beneficial inembodiments that do not use a resilient, stretchable material for theballoon 80.

As explained above, exposure of the esophageal mucosa to acid, e.g.,gastric acid and digestive enzymes from the stomach S or duodenum (notshown), for abnormal times or at abnormal levels, typically results intissue damage, which is manifested in varying degrees of mucosal damage.Milder damage levels are not detectable with routine visual endoscopicexamination, while more advanced damage is endoscopically visible asvarying degrees of esophagitis or Barrett's esophagus. Exposure of theesophageal mucosa to acid for more than approximately 4.2% of the timeposes a significant risk of mucosal damage. Mucosal damage may take theform of microscopic mucosal defects, which are sometimes called “dilatedintracellular spaces” or “DIS” for short. Such dilated intracellularspaces provide greater access of luminal refluxate H⁺ ions tonociceptors within the esophageal mucosa, thereby serving as a basis forenhanced chemoreceptor perception of refluxate, thus pain. Theesophageal epithelium of a healthy esophagus provides a structuralbarrier, which resists the diffusion of refluxed and ingested materialsthrough the mucosa. Abnormal exposure of the esophageal epithelium toreflux of acid, pepsin, and bile from the stomach or duodenum can resultin damage to the cellular junction complex of the esophageal epithelium.The increased salt and water flow allowed by these compromised cellularjunctions result in further damage and the eventual development ofdilated intracellular spaces in the epithelium. Dilated intracellularspace is a recognized morphologic feature in both GastroesophagealReflux Disease (GERD) and Non-Erosive Reflux Disease (NERD) patients.Non-Erosive Reflux Disease patients are patients with abnormalesophageal acid exposure, but who still have visually normal esophagealmucosa, as determined by routine endoscopic examination. While notvisually recognizable with routine endoscopy, dilated intracellularspaces are an effective early marker of epithelium damage secondary toreflux disease.

In patients with dilated intracellular spaces, the potential differencechanges of esophageal tissue with acid perfusion reflect elevated ionpermeability of the mucosa. The example mucosal impedance probe 10 withthe inflatable balloon 80 for pushing the impedance sensor electrodes 40into direct contact with the interior wall 84 of the esophagus E, asdescribed above, enables a direct measurement and sensitive assessmentof mucosal (epithelial) impedance. By virtue of direct contact of animpedance electrode 40 with the esophageal mucosa, highly accuratedeterminations of impedance can be made, thereby providing a basis foridentification of patients with compromised esophageal mucosa withoutthe need for biopsy and electron microscopy, which was not possible withconventional Multichannel Intraluminal Impedance (MII) reflux monitoringstudies for reflux activity detection, because such conventional MIImeasured values are highly variable and nonspecific to detection ofmucosal conditions. Such variability and non-specificity of conventionalMII testing is due to differences in conductivity of any air, liquid, orconductive material in the esophagus lumen, and the apparatus andmethods of this invention minimize or eliminate such variability andnon-specificity, as explained above.

An example embodiment of a mucosa impedance measuring system 100 forimplementing mucosa impedance measuring with a mucosa impedancecatheter, such as the example mucosal impedance catheter 10 describedabove, is illustrated in the function block diagram of FIG. 5. Othercatheter types or structures can also be used, as explained below, withthis example system 100. This example mucosal impedance measuring system100 includes a catheter, for example the catheter 10 described above,for being positioned in a patient's esophagus in a manner to measureesophageal mucosal impedance at numerous longitudinally spaced locationsof the esophageal mucosa, for example, but not for limitation, at onecentimeter spacing as described above (FIG. 1). As also explained above,the example catheter 10 includes a balloon 80 that is designed toexpand, e.g., by inflation, once placed in the esophageal lumen, so thatthe impedance sensors 40 on the peripheral surface of the catheter 10are placed in direct contact with the esophageal mucosa. In this manner,impedance measurements can be made that measure the impedance of theesophageal mucosa between the selected ones of the impedance sensors 40.A catheter activator 104 in FIG. 5 controls the inflation and deflation,thus expansion and contraction, of the balloon 80. The activation andinflation of the balloon 80 on catheter 10 is a controlled process.Enough pressure has to be applied so that the impedance sensors 40contact the esophageal mucosa with sufficient force to obtain accurateimpedance readings, but without creating an excessive deploymentpressure, which could damage the patient's esophagus E. Also, excessivepressure on the tissue can cause the impedance of the tissue to change,so controlled pressure is also desirable to minimize or avoid contactpressure based impedance value variations.

As also illustrated in FIG. 5, processing electronics 106 create sensorsignals 110 to the electrodes 40 and obtain the impedance measurementsresulting from such signals 110, as explained above. Other sensor datamay also be acquired, such as pressure sensor data from one or morepressure sensors and data from other sensors that may be disposed in thecatheter 10 (e.g., optional pressure sensor 35) or in connectingportions to catheter 10 (e.g., pressure sensor 212 in FIG. 6). Theprocessing electronics 106 creates sensor impedance data 114 and anyother data that is applied to computer 112. The computer 112 furtherprocesses the data and generates display data in any of a variety ofdisplays, e.g., graphical, maps, numbers, images, sounds, and otherknown data display formats, any or all of which are representedgenerically in FIG. 5 by the display function 118.

The computer 112 also generates a control signal 122 that controls theprocessing electronics 106. For example, computer 112 may generatecontrol signals to perform various different types of impedancemeasurements, e.g., at different locations or channels or with differentvoltage or current levels, and could repeat or re-try variousmeasurements. Computer 112 also generates control signal 116 thatcontrols the catheter activator 104. For example, computer 112 mayprovide an activation control signal 116 to the catheter activator 104to inflate or deflate the balloon 80 of the catheter 10. In addition,control signal 116 may control the pressure in a pneumatic type ofcatheter 10, which may be adjusted during various impedancemeasurements, as detected by computer 112, to obtain additional sensordata. The computer 112 can be any form of computer, microprocessor, orother device or devices programmed to perform the functions describedherein, as would be understood by persons skilled in the art. A userinput function or device 120 can be connected to computer 112 to enablea user to input commands, data, and other information and to controlcomputer 112. Catheter activator 104 may also include override safetydevices that do not allow the balloon 80 to be inflated beyond a certainamount, or to create a pressure greater than a predetermined pressurewithin the balloon 80.

FIG. 6 is a more detailed block diagram of an example embodiment of amucosal impedance measuring system 200. As illustrated in FIG. 6, theexample catheter 10 is shown with the balloon 80 inflated as it would beafter it is inserted into and esophagus E (not shown in FIG. 6) andready for taking mucosa impedance measurements with the electrodes 40,as described above. Again, other catheter embodiments can also be usedwith this system, another example of which is described in more detailbelow. As indicated above, any desired method can be used for inflatingthe balloon 80. Even a simple syringe assembly (not shown) could beconnected to the tube 12 (FIGS. 1-4) or to the tubing 208 in FIG. 6 topush air into the balloon 80 to inflate it and could be pressurecontrolled by a relief valve preset to the upper limit of a safeinflation pressure. The syringe plunger assembly can be moved in areverse direction to remove air or fluid from the system to controlballoon deflation prior to extubation. The tubing 208, which houses thewires 85 as well as conducts the air or other fluid under pressure tothe balloon 80, may comprise surgical tubing that is connected to a pump216 for pumping air or other fluid into the balloon 80. A pressurerelief valve 248 comprises a safety relief valve that ensures that thepressure in tubing 208 and in the balloon 80 does not exceed apredetermined maximum level, which may cause damage to the patient'sesophagus or adversely influence impedance readings. In addition, apressure sensor 212 is disposed in, or connected in fluid-flow relationto, the tubing 208 to measure the air pressure in tubing 208, so thatthe pump 216 can be controlled and not over inflate the balloon 80. Thepressure sensor 212 can also be used to monitor pressure for positioningthe catheter 10 in a desired location in the esophagus, as describedabove. Plurality of wires 83 (FIGS. 3 and 4) in the bundle 85 areconnected to the plurality of impedance sensor electrodes 40, as alsodescribed below.

As also illustrated in FIG. 6, an electrical isolation and signalconditioner circuit 220 provides electrical isolation for the pressuresensor wires 214, impedance sensor wires 85 and the AC power 218 that isapplied to the air pump 216. AC power 222 is applied to the isolationand signal conditioner 220, which generates the isolated AC power signal218 that is used to run the pump 216. Electrical isolation and signalconditioner 220 may contain signal conditioning circuits that adjust thesignal properties of the impedance sensor signals on impedance sensorwires 85, as well as other sensor signals. The adjusted sensor signals226 are then applied to processor 234. Adjusted pressure signals 224 areapplied to processor 232, which processes the pressure signals 224 andgenerates pressure data 236 that is applied to the computer 244.Pressure control signals 238 are generated by computer 244 and appliedto processor 232 which generates control signal 230 in response to thepressure control signals 238. In response to the control signal 230, thecontroller 228 generates a pressure pump control signal 252 to controlthe pressure pump 216 to inflate the balloon 80 for the purposesdescribed above. Alternatively, the tubing 208 could simply be connectedto a pressurized air or other pressurized fluid system (not shown), inwhich case a regulator valve (not shown) could be used to turn on andoff pressurized fluid flow to the balloon, as would be understood bypersons skilled in the art, once they understand this invention.

The signals 238 from the computer 244 also include signals processed bythe processor 232 to generate control signals 231 to a controller 229,which generates control signals 253 to a discharge valve 255 to open andclose the discharge valve 255. Opening the discharge valve 255 releasesthe air or other fluid pressure in the tubing 208 and deflates theballoon 80. The computer 244 can use the pressure data 214 from thepressure sensor 212 to monitor and control the pump 216 and thedischarge valve 255 to inflate the balloon 80 to a pre-set appropriatepressure and maintain it there during impedance measuring operations andto deflate the balloon 80 when the impedance measuring operations arecompleted.

If desired, especially, but not necessarily only, when a non-resilient,non-compliant, and minimally conductive or non-conductive balloon 80material, for example Mylar™ or polyolefin, is used, the pump 216 can bereversible and used to evacuate air or other fluid from balloon 80 to besure it is fully deflated and collapsed before attempting to pull thecatheter 10 out of the esophagus E. The processor 232 can respond tosignals from the computer 244 to generate the control signal 231 to thepump controller 228 to generate a pump control signal 265 to reverse thepump 216 to evacuate the balloon 80.

The computer 244 also uses the pressure data 214 to output a signal 257to an indicator 259 to notify the user whether the balloon 80 is fullydeflated, thus safe for insertion into, or extraction from, theesophagus as well as to notify the user when the balloon is inflated tothe proper pressure for the impedance measuring operations. Suchnotification can be visual, audible, or any other convenientnotification. Processor 234 processes the isolated sensor signals 226and generates sensor data 240 that is applied to computer 244. Thesensor data is further processed by the computer 244 and displayed ondisplay 242. The display 242 is generic and can include any or all ofvisual, audible, graphic, paper, electronic, or other types of displaysknown in the art. The indicator 259 could be combined with the display242, if desired.

Computer 244 may also generate control signals 241 that are applied toprocessor 234. Processor 234 processes the control signal 241 andgenerates signals 227 that are applied to the impedance electrodes 40via wires 85 to measure the impedance of the esophageal mucosa, forexample, but not for limitation, by measuring current flow at a constantvoltage, or vice versa, applied to the electrodes 40. Such measuringfunctions can be performed by the computer 244 or by the processor 234for any other component (not shown) that can be provided with thatcapability as would be understood by persons skilled in the art, oncethey understand this invention.

A user input device for function 246 is also provided for a user toprovide various inputs to the computer 244 to operate the system 200,change parameters, override automatic functions, choose and manipulatevarious displays, input patient data, and the like. Of course, personsskilled in the art will understand that the various functions of thecomputer and several processors can be combined or separated into one ormore devices, microprocessors, computers, and the like, all of which arestill within the scope of this inventions as described and claimed.

FIG. 7 is a work diagram illustrating an example of steps that can beperformed with the example catheter 10 and mucosa impedance measuringsystem 200 described above to obtain impedance measurements ofesophageal mucosa using the concepts illustrated by those and otherembodiments of this invention. As illustrated in FIG. 7, this exampleprocess starts at step 702. At step 704, input information regarding thepatient is entered by a user through a user input device, such as inputuser device 120 (FIG. 5) or user input device 246 (FIG. 6). At step 706,the catheter 10 is intubated and positioned within the esophagus E (forexample as illustrated in FIG. 2). This step can include monitoring theintra-esophageal pressure on the catheter 10 during insertion orintubation to determine when the catheter 10 is in a desired position orlocation in the esophagus E as described above. At step 708, the balloon80 is inflated to achieve direct electrode 40 contact with theesophageal mucosa on the interior wall 84 of the esophagus E (forexample as illustrated in FIG. 1). At step 710, the system (for example,100 in FIG. 5 or 200 in FIG. 6) monitors the balloon 80 pressure todetermine when balloon 80 has been inflated the desired or predeterminedamount to position the electrodes 40 in optimal direct contact withoptimal pressure against the esophageal mucosa. At step 712, the balloon80 inflation is stopped when the optimal balloon pressure is achieved,indicating that the catheter 10 is fully and properly deployed in theesophagus E. At step 714, the system 100 or 200 selects and queries theimpedance channels by sending impedance signals (e.g., voltage orcurrent) to the selected electrodes 40 (e.g., selected pairs of adjacentelectrodes 40) to assure signal quality prior to acquisition of data. Inaddition, these test signals can provide an indication as to whether thecatheter 10 is correctly deployed in the esophagus E or if adjustmentsneed to be made to either the pressure or position of the catheter 10.At step 716, mucosal impedance data is acquired, displayed, and recordedby the mucosal impedance measuring system, for example, the mucosalimpedance measuring system 100 (FIG. 5) or the mucosal impedancemeasuring system 200 (FIG. 6). After the data has been acquired, theballoon 80 of the catheter 10 is deflated and collapsed at step 718. Atstep 720, the pressure signals from a pressure sensor, such as pressuresensor 212, are read to ensure that the balloon 80 of the catheter 10 isfully deflated. Once it is determined that the balloon 80 is fullydeflated, the catheter 10 is extubated at step 722. At step 724, theprocess is stopped.

FIG. 8 illustrates and example software flow diagram 800 of one exampleembodiment of software that can be utilized in accordance with thepresent invention. As disclosed in FIG. 8, the process starts at step802. At step 804, the patient data is acquired. At step 806, controlsignals are generated to activate the catheter. At step 808, thepressure monitor signal (PMS) is monitored. At step 810, it isdetermined if the pressure monitor signal (for example the signal 214from pressure sensor 212 in FIG. 6) indicates a pressure that is greaterthan a predetermined maximum pressure. If the pressure monitor signalindicates a pressure that reaches that maximum level, the catheter isdeactivated at step 812 and the process is stopped at step 814, prior toany damage occurring to the patient. If the pressure monitor signal hasnot reached a maximum level, at step 816 the value of the pressuremonitor signal is determined. If the value of the pressure monitorsignal is low, the pressure is increased at step 818 and the process ofdetermining the pressure level, at step 816, is continued. Once thepressure reaches an optimal level, the process proceeds to step 820. Atstep 820, the pressure is maintained at the optimal pressure level. Thisoptimal pressure level may be achieved by continuously monitoring andadjusting the pressure level through control signals that control an airpump (e.g., the pump 216 in FIG. 6). At step 822, signals are generatedto detect the impedance of the esophageal mucosa. As indicated above,test signals may first be generated to determine if the proper pressureand adequate contact between the impedance sensor electrodes 40 and theesophageal mucosa exists. Adjustments may be made prior to reading theimpedance data. At step 824, the impedance data is detected. At step826, the impedance data is processed for display. At step 828, it isdetermined whether additional data should be collected and processed. Ifso, the process returns to step 824. If not, the process proceeds tostep 830. At step 830, a control signal is generated to deactivate anddeflate the catheter 10. The process then proceeds to step 832. At step832, the pressure signal is monitored to ensure that the catheter probeis deflated for extraction from the esophagus. The process is stopped atstep 834.

FIG. 9 is a work flow diagram 900 illustrating the manner in which thedata can be analyzed. At step 902, the collected data for a particularpatient is opened for study. At step 904, the acquired impedance data isviewed on a display, such as display 118 (FIG. 5) and display 242 (FIG.6). At step 906, the acquired data is analyzed to determine impedancevalues. In a simplified version, the data can be displayed as one ormore impedance values, or as a waveform at step 908. More complexanalyses can also be performed which may include other parameters suchas intraballoon pressure, and mucosal impedance relationships. Forexample, the acquired impedance data can be opened and then marked,deleted, or edited at step 910 in accordance with time periods when themucosal impedance is measured. The mucosal impedance data can then beanalyzed to measure baseline impedance for each respective channel andmean and median baseline impedance at each respective level of theesophagus. A display of the mucosal impedance baseline differences canbe graphically illustrated at the respective levels of the esophagus. Inaddition, plots can be generated that can illustrate the data in twodimensions or three dimensions, including, but not limited to, bargraphs, line graphs, contour plots, iso-contour plots, etc., and theycan be represented in colors for various values or features. The plotsmay include a graphical representation of the esophageal anatomy. Theplot can show the impedance as a function of its physical position inthe esophagus. Reports can be generated in textual form or graphicalform. The reports can be printed or simply saved in a database or aselectronic media. Normal values can be shown and abnormal results can beemphasized by highlighting, color change, font change, etc. Referringagain to FIG. 9, the data can then be provided to a clinician foranalysis at step 912. At step 914, an archive report can be generatedand stored. At step 916, the process is stopped.

As mentioned above, damaged esophageal mucosa is more conductive ofelectric current than healthy, undamaged esophageal mucosa. A proof ofconcept study was conducted using a simplified version of the catheterin FIG. 1 with a single impedance channel comprising two adjacentimpedance electrodes. The catheter including the two impedanceelectrodes was manually pressed to the esophageal mucosa after passagethrough the working channel of an endoscope. An initial mucosalimpedance measurement was taken in each test subject at a distallocation in the esophagus by reading the single mucosal impedancechannel at the first distal location and then sequentially pulling thecatheter upwardly specific distances to reposition the two impedanceelectrodes at successively more proximal locations and taking impedancemeasurements at each of the successively more proximal locations. Thecatheter was connected to a commercially available impedance detectionand recording system manufactured by Sandhill Scientific, Inc. Usingvisual guidance, the mucosal catheter was directly applied to theesophageal mucosa at two centimeters, five centimeters, and tencentimeters proximal to the gastroesophageal junction (LES). Whenendoscopically visible mucosal erosions were present, mucosal impedancereadings were also taken at the site of injury and annotated to quantifyesophagitis grade and/or Barrett's mucosa. In endoscopically negativepatients (i.e., patients with no visual evidence of mucosal erosion),data was acquired via ambulatory acid reflux monitoring to identifypatients with abnormal acid exposure. Research data from the 38 patientswas analyzed to determine 5-second mean mucosal impedance values at allesophageal test sites on each respective patient. Patient data wasanalyzed based on mucosal impedance test site, endoscopic erosioncategories, and acid exposure categories. The purpose of the study wasto determine if there were mucosal impedance differences in patientswith endoscopically normal esophageal mucosa versus patients withesophagitis and Barrett's esophagus. The results of the study showedthat, of the 38 test subjects, 13 were esophagitis positive, 9 hadBarrett's esophagus, and 16 were endoscopically negative. Of the 16endoscopically normal subjects, 7 underwent ambulatory pH monitoring toquantify acid exposure. Impedance values in visually normal esophagealmucosa at the 2, 5, and 10 centimeter locations had significantly higherimpedance than esophagitis (E+) and Barrett's Esophagitis (BE) sites, asshown in FIG. 10, indicating that non-eroded tissue can bedifferentiated from eroded tissue using mucosal impedance. In patientswith visually normal tissue and normal acid exposure, impedance at the2, 5, and 10 centimeter locations had only small variations, as shown inFIG. 11. In patients with visually normal tissue and abnormal acidexposure, commonly referred to as non-erosive reflux disease (NERD),impedance at the 2, 5, and 10 centimeter locations had significantvariation with progressively lower impedance moving from proximal todistal sites, as also shown in FIG. 11. Conclusions drawn from thisstudy include the following:

1.) In endoscopically positive patients with visually identifiabledamage to the esophageal mucosa, damage is more pronounced in the distalesophageal and progressively less pronounced moving from the distal toproximal esophagus in parallel to the visual observation of mucosaldamage suggesting that mucosal impedance measurements could be analternative marker for GERD. In this patient category, mucosal impedanceis 50% to 80% lower in the distal esophagus than in the proximalesophagus validating that mucosal impedance variation in excess of 50%along the length of the esophagus is a marker of pathologic GERD, thusis usable as a difference criteria for GERD.

2) In endoscopically normal patients lacking visually identifiablemucosal damage, two distinct patient categories of mucosal impedancefindings are shown:

a.) Visually normal patients with normal acid exposure as measured withambulatory reflux monitoring have insignificant mucosal impedancevariations of less than 20% along the length of the esophagus fromdistal to proximal. This finding suggests that in patients with lessacid reflux (within normal pH parameters) the degree of change inmucosal impedance along the esophagus is less variable than in thosewith visual mucosal damage or in those with abnormal acid refluxparameters and is usable as a difference criteria for healthy mucosaltissue.

b.) Visually normal patients with abnormal acid exposure as measuredwith ambulatory reflux monitoring have significant mucosal impedancevariations of greater than 40% along the length of the esophagus, thusis usable as a difference criteria for NERD. This finding supports thatmucosal impedance measurements may be a sensitive means of defining notonly visual damage (GERD) but also chronic acid reflux in those withoutvisual mucosal damage (NERD).

In summary, these results show that mucosal impedance, which is theinverse of mucosal conductivity, is reduced in damaged esophageal mucosaas compared to healthy esophageal mucosa. The data indicate that suchimpedance reductions are in the range of 50 to 80 percent whenesophageal mucosa is damaged, thereby supporting the ability of thisinvention to make sensitive detections of damaged tissue. Additionally,as illustrated in FIG. 12, mucosal impedance is significantly morevariable along the axial length of the esophagus in patients withesophageal damage. In the reflux damaged esophagus, impedancemeasurements in the distal esophagus (i.e., farther from the mouth andcloser to the stomach) are significantly lower than in the proximalesophagus. This distinct variation in mucosal impedance along the axiallength of the esophagus may be attributed to progressively greaterexposure to damaging reflux fluids from the stomach or duodenum in thedistal esophagus versus the proximal esophagus. In undamaged mucosapatients, minimal mucosal impedance changes occur axially along thelength of the esophagus as compared to significant changes in refluxdamaged patients. These phenomena support the sensitive assessment ofmucosal damage both as discreet impedance values and as extent ofimpedance changes, i.e., impedance differences, between distal andproximal levels along the axial length of the esophagus.

As mentioned above, a more complex analysis involves a relationshipbetween intraballoon pressure and mucosal impedance. More specifically,mucosal impedance changes as the pressure with which the impedancesensors are forced into the mucosa changes, and damaged tissue is moresusceptible to impedance changes when the electrodes are pressed intothe mucosa surface than healthy tissue. Therefore, the extent to whichmucosa impedance changes as a function of pressure applied by theelectrodes on the mucosa is also an indicator of tissue damage. In aplot of impedance versus application pressure, normal tissue has arelatively flat plot line, e.g., not much change in impedance asapplication pressure increases, whereas damaged tissue has a plot linethat increases more sharply, i.e., larger changes in impedance asapplication pressure increases. Application pressure, i.e., the pressureat which the electrodes are pressed against the surface mucosa can bemonitored by the pressure in the balloon 80 that pushes the electrodes40 against the mucosa. Therefore, for example, if more proximal channel48 impedance measurements remain relatively unchanged or minimal changeas pressure in the balloon is increased, while more distal channel 48impedances decrease more sharply as pressure in the balloon isincreased, the indication would be a likelihood of gastroesophagealreflux disease, where, as explained above, more distal portions of theesophagus typically have more mucosal damage than more proximal portionsdue to more frequent acid reflux exposure. Therefore, differences inimpedance changes in different channels 48 located axially higher andlower in the esophagus as a function of balloon 80 pressure changes isindicative of healthy or damaged mucosa. Also, larger impedance changesin distal channels than in proximal channels as a function of changes inapplied pressure in the balloon are indicative of gastroesophagealreflux disease.

Another example embodiment of a mucosal impedance measuring catheter1310 is illustrated diagrammatically in FIGS. 13-16 for morecomprehensive mucosa impedance measuring and mapping. This examplecatheter 1310 has not just one axial row of impedance sensor electrodes40 as shown and described above for the example catheter 10 in FIGS.1-4, but multiple axial rows of electrodes 1340 at a multitude ofangular locations about the periphery of the catheter 1310. Therefore,when the catheter 1310 is positioned in the esophagus E and inflated topress the multiple axial and angularly dispersed electrodes 1340 againstthe mucosa on the interior wall 1384 of the esophagus E, as illustratedin FIG. 13, the electrodes 1340 contact multiple locations of the mucosaat divers locations longitudinally up and down and angularly around theinside wall 1384 of the esophagus E. As such, the impedance of themucosa can be measured between any selected pair of the electrodes 1340in the same manner as described above for measuring the impedancebetween any pair of the electrodes 40 of the catheter 10 in FIGS. 1-4.While not necessary, there are advantages to making each impedancechannel to measure impedance between pairs of adjacent electrodes 1340,for example, for accurate impedance measurements at concise locationsfor usefulness in analyzing and mapping the mucosa for healthy versusdamaged epithelial tissue.

Referring now primarily to FIGS. 14 and 16, the catheter 1310 comprisesa thin, flexible, balloon 1380 mounted around a length of a thin, innertube 1312, as best seen in FIG. 16. The inner tube 1312 is stiff enoughto be pushed into an esophagus E, carrying along with it the thin,flexible balloon 1380 when the balloon 1380 is deflated and collapsed,as shown in FIG. 15, but soft and flexible enough to minimize likelihoodof injury to the esophagus as the catheter 1310 is being pushed into theesophagus during intubation. The inner tube 1312 also has one or moreholes 1392 through its wall inside the balloon 1380 so that pressurizedair or other inflating fluid pumped into the lumen 1356 of the innertube 1312 is directed into the balloon 1380, as indicated by the flowarrows 1387, 1388 in FIG. 16, to inflate and expand the balloon 1380 inthe esophagus E as shown in FIG. 13 to press the electrodes 1340 on theperipheral surface of the catheter 1310 into direct contact with themucosa for acquiring the esophageal mucosa impedance measurements. Theinflation air or other fluid can also be released or evacuated from theballoon 1380 through those holes 1392 to deflate and collapse theballoon 1380, as illustrated in FIG. 14, before the catheter 1310 ispulled out of the esophagus E. The balloon 1380 material can be adheredor otherwise fastened in a leak-proof manner to the inner tube 1312, asindicated at 1313 and 1315 in FIG. 16. A flexible, resilient, distal endcap 1317 can be mounted on the distal end of the tube 1312, as shown inFIG. 16, to help seal the balloon 1380 to the distal end of the innertube 1312 or to seal the distal end of the inner tube 1312, as best seenin FIG. 16, as well as to help guide the tube 1312 into and through theesophagus during intubation.

The mucosal impedance sensor electrodes 1340 can be fastened to diverslocations axially up and down and angularly around the exterior surfaceof the balloon 1380 in any convenient manner. The thin, flexible,printed circuit boards 1330, each comprising multiple impedance sensorelectrodes 1340, shown in FIGS. 14, 16, is one example electrode 1340mounting structure that mounts the electrodes 1340 at divers locationslongitudinally up and down and angularly around the balloon 1380. Thethin, flexible, printed circuit boards 1330 can be made of any thin,flexible, electrically non-conductive material, for example, Mylar™ orpolyolefin, that conforms with the inflated expansion and deflatedcollapsed conditions of the balloon 1380. The thin, flexible, printedcircuit boards 1330 can include electric traces 1332 to connect theindividual electrodes 1340 on the printed circuit boards 1330 toimpedance signal generating and acquisition systems, for example, butnot for limitation, those shown in FIGS. 5 and 6 and described above.Any number of printed circuit boards 1330 can be used, or the balloon1380 itself can be made as a unitary printed circuit board.

The catheter 1310 has all of the functionalities described above inrelation to the in-line electrode catheter 10 and systems 100 and 200described above, but with more electrodes 1340 and electrode pairchannels available, especially dispersed both longitudinally andangularly around the periphery of the balloon 1380. The electric traces1332 of the printed circuit boards 1330 can be connected to theimpedance signal generating and acquisition systems, e.g., 100, 200, inany convenient manner, for example, but not for limitation, via theribbon wires 1334 shown in FIGS. 14 and 16 comprising multiple strandsof individual wires or conductors. As another example, elongatedextensions (not shown) of the thin, flexible, printed circuit boards1330 themselves could contain the traces extended all the way to thesignal generating and processing systems (e.g., 100, 200) outside thepatient's body and generally outside the catheter 1310. As also shown inFIGS. 14 and 16, the inner tube 1312 and ribbon wires 1334 (orsubstitute elongated extensions of the printed circuit board) are housedin an outer catheter tube or sleeve 1336, which is long enough to extendfrom the balloon 1380 in the esophagus E to the outside of the patient'sbody. The upper or proximal end portions 1385 of the balloon 1380 canalso be gathered and secured into the proximal end of the outer cathetertube 1336 for neatness and additional fastening of the balloon 1380 tothe inner tube 1312, and then a sealer 1338 can be applied or injectedinto the distal end of the outer tube or sleeve 1336, as shown in FIG.16.

As mentioned above, the mucosal impedance catheter 1310 with itselectrodes 1340 dispersed longitudinally and angularly on the surface ofthe balloon 1380 of the catheter 1310 provides a number of additionaldata sources, impedance measurements, and mapping points of a patient'sesophagus for determining existence, location, and extent of damage inthe esophagus. For example, a representation of various impedances fromnumerous test locations in a patient's esophagus can be viewed inthree-dimension graphical images (not shown) or unwrapped for bettervisibility of the results, as illustrated in FIG. 15. For example, the X(vertical) coordinate or edges can represent the distance from the loweresophageal sphincter (LES) at which a particular impedance value wasobtained or some other reference point, and the Y (horizontal)coordinate or edges can represent the distance around the circumferenceof the esophagus, relative to some reference point. Scalar values (e.g.,“+” or “−”) of the impedance data can then be plotted on the twodimensional chart, for example as shown on the chart in FIG. 15. Shadingor colors (not shown) can also provide a visual representation of thescalar values with any number of shades, intensities, or variations forany number of scale values.

The foregoing description of the invention has been presented forpurposes of illustration and description. It is not intended to beexhaustive or to limit the invention to the precise form disclosed, andother modifications and variations may be possible in light of the aboveteachings. The embodiment was chosen and described in order to bestexplain the principles of the invention and its practical application tothereby enable others skilled in the art to best utilize the inventionin various embodiments and various modifications as are suited to theparticular use contemplated. It is intended that the appended claims beconstrued to include other alternative embodiments of the inventionexcept insofar as limited by the prior art.

What is claimed is:
 1. A mucosal impedance measuring apparatus fordetecting and measuring a condition of mucosa, the mucosal impedancemeasuring apparatus comprising: a catheter comprising a tube; impedancesensing electrodes on an exterior surface of the catheter; a balloonmounted on the tube, the balloon being capable of inflation anddeflation; and an impedance measuring system including a processor, theimpedance measuring system adapted to measure a pressure-regulatedimpedance measurement of the mucosa that is indicative of the conditionof the mucosa when the balloon is inflated and the impedance sensingelectrodes direct an electric current through the mucosa while theballoon is pressed against the mucosa.
 2. The mucosal impedancemeasuring apparatus of claim 1, wherein the tube also has an interiorlumen and a hole through a wall of the tube that places the interiorlumen in fluid communication with the balloon and wherein the mucosalimpedance measuring apparatus further comprises an inflation anddeflation system connected to the tube for directed inflating gas intoand out of the balloon via the interior lumen of the tube, the inflationand deflation system comprising a controller.
 3. The mucosal impedancemeasuring apparatus of claim 2, wherein the impedance sensing electrodesare located on at least two thin flexible circuit boards which areangularly spaced around an exterior surface of the balloon.
 4. Themucosal impedance measuring apparatus of claim 2, wherein the balloonsurrounds the tube and the impedance sensing electrodes are positionedon an exterior surface of the balloon.
 5. The mucosal impedancemeasuring apparatus of claim 4, wherein the impedance sensing electrodesare positioned at divers locations on the exterior surface of theballoon.
 6. The mucosal impedance measuring apparatus of claim 5,wherein the impedance sensing electrodes are positioned in diversaxially and angularly spaced locations on the exterior surface of theballoon.
 7. The mucosal impedance measuring apparatus of claim 6,including a flexible printed circuit board comprising the impedancesensing electrodes mounted on the exterior surface of the balloon. 8.The mucosal impedance measuring apparatus of claim 2, wherein theinflation and deflation system is configured to inflate the balloon to apressure and maintain the balloon at the pressure during measurement ofthe pressure-regulated impedance measurement of the mucosa by theimpedance measuring system.
 9. The mucosal impedance measuring apparatusof claim 1, wherein the impedance of the mucosa as measured is dependenton a pressure with which the balloon presses the impedance sensingelectrodes against the mucosa.
 10. The mucosal impedance measuringapparatus of claim 1, wherein the impedance measuring system is furtheradapted to identify the mucosa having tissue characteristics of anesophageal disease based on the pressure-regulated impedance measurementof the mucosa.
 11. The mucosal impedance measuring apparatus of claim10, further comprising a display that is configured to spatially mapareas of healthy mucosa versus areas of damaged mucosa as determined bythe impedance measuring system.
 12. The mucosal impedance measuringapparatus of claim 1, wherein the impedance measuring system inelectrical communication with the impedance sensing electrodes.
 13. Themucosal impedance measuring apparatus of claim 1, wherein the impedancemeasuring system is configured to provide the electric current directedthrough the mucosa.
 14. A mucosal impedance measuring apparatus fordetecting and measuring a condition of mucosa, the mucosal impedancemeasuring apparatus comprising: a catheter; impedance sensing electrodeson an exterior surface of the catheter; means for pressing the impedancesensing electrodes against spaced locations on the mucosa; and animpedance measuring system including a processor, the impedancemeasuring system adapted to measure a pressure-regulated impedance ofthe mucosa that is indicative of the condition of the mucosa when theimpedance sensing electrodes direct an electric current through themucosa while the means for pressing the impedance sensing electrodespress the impedance sensing electrodes against the mucosa.
 15. Themucosal impedance measuring apparatus of claim 14, wherein the means forpressing the impedance sensing electrodes include a balloon beingcapable of inflation and deflation.
 16. A mucosal impedance measuringsystem, comprising: a catheter comprising: an inflatable balloon orbladder that is formed in a substantially cylindrical shape; impedancesensing electrodes disposed on an outer surface of the inflatableballoon or bladder; a catheter activator that expands the catheter sothat the impedance sensing electrodes contact mucosa, the catheteractivator including a controller; processing electronics that generateimpedance measuring signals and detect impedance signals generated bythe mucosa that are transmitted through the impedance sensing electrodesto generate impedance data that are taken under regulated pressure andwhich are indicative of a condition of the mucosa; a computer thatprocesses the impedance data.